Tick interactome and regulome in response to Anaplasma phagocytophilum infection

Resumen del trabajo presentado al V. Labuda's days, celebrado en Smolenice (Slovakia) del 12 al 14 de septiembre de 2018.Anaplasma phagocytophilum is an obligate intracellular bacterium vectored primarily by Ixodes spp. that causes various forms of granulocytic anaplasmosis in humans and animals. During tick feeding, A. phagocytophilum initially infects midgut cells and then subsequently develops in other tissues including hemocytes and salivary glands for transmission to susceptible hosts. As other intracellular pathogens, A. phagocytophilum develops within membrane-bound inclusions in the tick cell cytoplasm, where they evade and manipulate host cell response to limit pathogen infection and multiplication. In an ongoing evolutionary arms race, both A. phagocytophilum and tick cells have developed molecular mechanisms to ensure tick survival and pathogen infection and transmission. Recent insights into these mechanisms have shown that A. phagocytophilum induces tick proteins that increase tick survival, feeding fitness and vector competence while causing global tissue-specific changes in tick cell interactome (protein-protein physical and functional interactions) and regulome (transcription factors-target genes interactions). Molecular and functional studies have shown that A. phagocytophilum uses pathogen-tick protein-protein interactions for infection and causes remodeling of the cytoskeleton, inhibition of cell apoptosis, subversion of carbohydrate metabolism and oxidative stress, manipulation of the immune response and control of cell epigenetics to facilitate infection. Simultaneously, tick cells activate molecular mechanisms such as apoptosis, immune response and different metabolic pathways to limit pathogen infection and preserve fitness. Furthermore, recent research has demonstrated that A. phagocytophilum uses common strategies but affecting different molecular mechanisms for infection in both vertebrate and tick cells. Targeting some of these mechanisms may results in new strategies for the control of A. phagocytophilum and its associated diseases.Peer Reviewe